CN1477054A

CN1477054A - Microstructure manufacture and microsystem integration

Info

Publication number: CN1477054A
Application number: CNA031367321A
Authority: CN
Inventors: 黄智礼
Original assignee: Individual
Current assignee: Individual
Priority date: 2002-05-15
Filing date: 2003-05-15
Publication date: 2004-02-25
Anticipated expiration: 2023-05-15
Also published as: US7125510B2; CN100427378C; US20030214057A1

Abstract

Fabrication of a microstructure device includes assembling a mold component and a mold body to form a device mold for the microstructure device. The microstructure device is cast from the device mold, then the mold component is removed from the microstructure device. The microstructure device is then released from the mold body.

Description

Micro-structural manufacturing and micro-system are integrated

One, technical field

The present invention relates to micro-structural manufacturing and micro-system integrated technology.

Two, background technology

Little bulk analysis system, (μ Tas) also claims lab-on-a-chip system (Lab-on-a-chip), micro-fluid chip and MEMS (MEMS) is integrated into the device of a miniaturization.Little bulk analysis system has been used for chemistry and bioanalysis, electrophoresis for example capillaceous (CE), and flow cytometry, liquid chromatogram (LC) and mass spectrum (MS), little bulk analysis system also is used for chemistry and medicine synthesizes, clinical diagnosis.The manipulation and the analysis of fluid samples comprise microfluidic device in little bulk analysis system, as the microchannel, and little valve, Micropump, and blender.Because little bulk analysis system device is integrated on the very little chip, only Wei Liang fluid and sample are used to analyze.This improves the performance of system widely and reduces sample, the cost of reagent and analysis.

Three, summary of the invention

Say that integrally feature of the present invention is to set forth a method of making micro structural component, comprising a model element of combination and a mould body is a device mould, from micro element of device die casting, removes the model element and the demoulding from micro element.Specializing of invention can comprise following feature: with liquid polymers from device die casting one micro structural component; Liquid polymers can add additive or particulate to change its characteristic.Liquid polymers comprises: polyurethane, polydimethylsiloxane, Merlon, polypyrrole, resin, teflon resin, epoxy resin, the rubber of polymerization or the plastics of polymerization.

But model element can be rigidity model or casting pattern.But the casting pattern element can adopt and can reverse the material manufacturing, and the model element that it is solid-state can be from solid-state liquid state or the gaseous state of transferring to when one or more environmental factors change.After the micro structural component casting, therefrom remove model element and can comprise the one or more environmental factors of change, thereby can reverse the material model element from solid-state liquefy.Remove model element and can comprise applying centrifugal force or vacuum draw, separate the liquid model element in the micro structural component.Reversible model element also can adopt the sublimator material manufacturing, can be from the solid-state gaseous state that transfers to when environmental factor changes.Remove model element and can comprise and change one or more environmental factors, so model element changes gaseous state into and separates from micro element from solid-state.Model element can also adopt the soluble material manufacturing, and it can form a solid-state shape also can be by a specific dissolution with solvents.

Model element can comprise cured, gel, fusible alloy, eutectic alloy, resin, lipid or amine salt.The physical dimension of model element is less than 5 millimeters.The shape complementarity of the shape of model element and the micro-structural of constructing in micro structural component just is formed in the micro structural component in the shape of model element after separating model element from micro structural component.Model element can comprise an element that elongates shape and be used for forming a microchannel at micro structural component.The micro-structural of other shape can be come the modeling element by using component mold.

The modeling element can be poured the material of liquid state in the component mold into, changes one or more environmental factors and liquid material is become be solid-state or gel.The shape of component mold is consistent with the model element shape that will make, by the injection molding form liquid material is injected mould and forms model element or by pressing mold dusty material is pressed into model element.

On the other hand, the present invention has presented the method for making micro structural component, and this comprises a set of model element and set of molds are fitted together, casting micro structural component and from micro structural component model element is taken out.

Of the present invention specializing comprises following one or more feature:

The casting micro structural component comprises that casting or injection molding liquid polymers are in the device mould, one set of model element comprises two model elements, the shape of first model element is used for producing first cavity at micro structural component, the shape of second model element is used for producing second cavity at micro structural component, certain interval is arranged between first and second the model element when assembly jig, thereby form a flexible barrier film between two corresponding cavitys in micro structural component.One set of model element also comprises two and elongates the shape model element, and the size of first model element or diameter are less than second model element.The centre of the model element second has an aperture can pass first model element.When the assembly device mould, first model element is passed in the aperture on second model element and forms one and cross, and after the micro structural component casting, two are elongated the shape model elements and remove from device, have just formed two passages with joint in device.

One set of model element also can comprise one and elongate shape model element and a tubular model element, and the inside dimension of tubular model element or internal diameter are consistent with the size or the external diameter of elongation shape model element.When assembly jig, elongate the shape model element and insert in the tubular model element, after removing mould, in micro structural component, just formed the passage of a size or internal diameter varies.

One set of model element also can comprise the model element that can cast and an elongation shape model element, the model element that can cast is used for being used to form a passage that connects cavity from the outside at identical shaped cavity of micro structural component structure and elongate the shape model element.It is an end that is used to accept to elongate the shape model element that but a dolly dimple is arranged on the casting pattern element.One key tooth is arranged in dolly dimple, at an end that elongates the shape model element corresponding keyway is arranged, this key teeth groove structure is used for preventing both moving mutually or rotating when mould is assembled.

One aperture is arranged on the wall of mould body.But an end that elongates the shape model element inserts the depression on the casting pattern element.The other end passes the aperture on the wall.Also there are corresponding key toothing and the keyway that elongates on the shape model element to be harmonious in the aperture.Model element rotates or moves when preventing the mould assembling.

Aperture on the mould body wall has played the purpose of support model element and fixed model position of components.Other components and parts in itself and the microstructure device are cooperatively interacted.

One set of model element also can comprise a column structure, and when model element was assembled, the column structure model element played the effect of support elongated shape model element, makes it be fixed on the position of design.

From another angle, the present invention has stated the method for producing micro structural component of making, comprise combination one a set of model element and a cover function element and form the device mould, the casting micro structural component, disjunctive model element from micro structural component and reservation function element have realized having the integrated device of function element and micro-structural thus in micro structural component.

The present invention is embodied in following several aspect: the casting micro structural component can comprise to be poured liquid polymer or the injection device mould into.But a set of model element can comprise the casting pattern element.Function element can comprise electrode.When the assembling device mould, but earlier electrode is imbedded in the casting pattern element, after the micro structural component casting, but the casting pattern element therefrom separate, but and the electrode that buries just is fixed in the cavity that stays after the casting pattern element separates.

But this cover casting pattern element can comprise elongation shape model element, and function element can comprise ring electrode, the size of ring electrode interstitial hole and the tangent plane consistent size of elongating the shape model element.When the assembling device mould, the interstitial hole that the shape model element inserts ring electrode will be elongated.Behind the casting micro structural component, from micro structural component, separate and elongate the shape model element, ring electrode is just imbedded in the micro structural component and with the passage that is formed by elongation shape model element and is contacted.

The passage that is formed by elongation shape model element also can be used for the liquid light guide passage.On channel surface, be coated with the last layer refractive index less than the liquid refractive index that is fed in the passage, just form the liquid light guide passage.

The device that the present invention presents comprises having the micro structural component body of microfluidic channel, be imbedded in the micro structural component with liquid contacting electronic element and the electronic device that is attached thereto, transmit and accept the optics of light.

The present invention specializes and to show the following aspects, and the micro structural component body is made by polymer, and fixedly electronics and optics are at the platform of ad-hoc location to comprise one in the device, and this platform can be a circuit board.

The passage that in micro structural component, forms a cavity and be attached thereto by aforesaid method, be equipped with a heater in cavity bottom, be used to heat the liquid that injects in the cavity, heater is by the little processing controls that is imbedded in the device, also be equipped with temperature sensor in the cavity, and link to each other, thereby realize control to fluid temperature in the cavity with microprocessor.This structure can be used for the PCR (PCR) of DNA in the micro structural component.

Optics integrated in micro structural component can comprise, lens, photoconductive channel, and optical sensor.Also can comprise the cavity of a little valve and the passage between inlet and cavity in the micro structural component, at the opening part of passage one diaphragm be arranged, can reach by moving of matrix and split or the purpose of closing passage, this matrix can be the memorial alloy sheet.Also can comprise a fluid intake and a cavity in the micro structural component, fluid intake is a funnel channel of inserting cavity, the part that funnel inserts in the cavity is a springform channel design, and the funnel opening bigger from top is to the springform passage, and its size is tapered.When fluid from outside enters cavity by inlet, this opening is opened, and when the pressure in the cavity during greater than the pressure of outside, this opening pressurized and closing.The fluid intake of realizing this unidirectional control can be to be realized by a film formed funnel shaped structure of elasticity.

The microfluid system that the present invention presents, comprise a microfluidic device and the cartridge of interfaces with it, specifically comprise following characteristic: integrated pneumatic power element in the microfluidic device, and in cartridge, comprise interface and the corresponding components and parts that are coupled with these pneumatic elements; Integrated electronics in the microfluidic device, and in cartridge, comprise interface and the corresponding device that is coupled with these electronic components; Be integrated with optical element in the microfluidic device and in cartridge, comprise interface and the respective optical element that is coupled with these optical elements.

Device mould of the present invention on the other hand comprises by mold, model element and function element to be formed.Mold, model element and function element are combined and are fixed in its design attitude when the assembling device mould.After the device casting, model element separates from the device mould with mold, and function element is integrated among the device.The present invention also is in particular in: but the model element of device mould is a cover casting pattern element comprise the first group model element and the second group model element, the first group model element is used for forming first group of cavity and passage at micro structural component, the second group model element is used for forming second group of cavity and passage at micro structural component, the position of first group of cavity and second group of cavity is a counter structure up and down, the middle elastic diaphragm that forms, this structure forms a peristaltic pump in micro structural component.The device mold go to the bottom and frame on some apertures are arranged, the position in its hole is used to determine when the device die assembly, the position of model element and function element.

Other characteristic of the present invention and advantage will be stated in figure and the claim in following description:

Four, description of drawings Fig. 1, the perspective view of a multi-layer cavity micro structural component.Fig. 2, the front view of a multi-layer cavity micro structural component.Fig. 3, the device mould top view of the multiplelayer microstructure device that is used to cast.Fig. 4, device die cut view Fig. 5 of the multiplelayer microstructure device that is used to cast is used in a model element perspective view in the device mould.Fig. 6, the top view of the component mold of the model element shown in Figure 5 that is used to cast.Fig. 7 and 8, two cutaway views of Fig. 6.Fig. 9, the perspective view of a multiple microchannels micro element.Figure 10, the top view of the device mould of the microchannel devices shown in Figure 9 that is used to cast.Figure 11-12, two cutaway views of Figure 10.Figure 13, the separation graph of a microfluid system.Figure 14, the top view of microfluidic device in the microfluid system.Figure 15 comprises the platform of a circuit board and function element in the microfluidic device.Figure 16, the process of manufacturing micro-structural microfluidic device.Figure 17, sample flows into the cutaway view of cell in the microfluidic device.Figure 18, the cutaway view of a wriggling Micropump in the microfluidic device.Figure 19, the cutaway view of a little valve in the microfluidic device.Figure 20, the liquid pool of a potting in the microfluidic device, the cutaway view of integrated electrode and two passages.Figure 21 is used to make the cutaway view of the device mould of Figure 20 part.Figure 22, the cutaway view of the electrode group of Electrochemical Detection and the position in micro structural component.Figure 23, one of them electrode of electrode group shown in Figure 22.Figure 24, the micro-structural cutaway view of laser-Induced Fluorescence Detection in the microfluidic device.Figure 25, with electronics in the microfluidic device, the cartridge of optics and fluid interface.

Five, the specific embodiment

Following definition will be employed in will describing below:

Can reverse material: for solid-state, when environmental factor changed, states of matter can change liquid into to material under the certain environment state.And when environmental factor was got back to previous state, it is solid-state that states of matter transforms back into again, and factor of environmental has temperature, pressure, magnetic field etc.Can reverse examples of material has; Gel, fusible alloy, eutectic alloy and resin.

Soluble material: be mainly matrix material, it at room temperature is solid-state, but when contacting with a solvent, can be dissolved.The example of soluble material has soap, cured, steroids and triglyceride.

Sublimator material: material is solid-state under a certain temperature or pressure, but increases or pressure when reducing when environment temperature, material transition gaseous state and evaporating.The example of sublimator material has amine salt, as ammonium chloride (NH ₄CL) be solid-state at normal temperatures, and be that 30 ℃ or pressure are that ammonium chloride is decomposed into ammonia and hydrogen chloride under the environment of 1.3mbar in temperature.

But casting model element: this class model element is by one or more materials that reverse, soluble material, or sublimator material is made.But micro-structural shape complementarity in the shape of casting model element and the quilt micro structural component of manufacturing, after micro structural component is manufactured, but the casting model element will break away from from micro structural component.

Elongate the shape model element: for thread, shaft-like or laminar.Very big for its height of laminar model element, wide ratio, both its length or width were much larger than its height or thickness.Elongating the shape model can be processed into by stainless steel, plastics or silicon, but also can adopt the method for manufacturing the casting model element to manufacture.

Fig. 1 and Fig. 2 show the perspective view and the front view of a multilayer inner chamber micro structural component 100 respectively.Fig. 3 represents to be used to cast the device mould 300 of micro structural component 100, Fig. 4 represent device mould 300 along the plane 4 profiles of cutting open.

Referring to Fig. 1-4, multilayer inner chamber micro structural component 100 is by 300 castings of device mould.Device mould 300 is mainly combined by following model element: mould body 301, but 2

casting model elements

210 and 310 and 4 elongation

shape model element

302a, 302b, 302c and 302d.Liquid polymer is poured in the cavity 304 in the mould body 301, after liquid polymers solidifies, elongates the shape model element and just extracts from device mould 300.If but

casting model element

210 and 310 is by reversing the material manufacturing, device mould 300 just can be heated to make and can reverse the temperature that material is melted to liquid, the reversed material of fusing is removed from micro structural component 100 through the passage that forms after being extracted by elongation shape model element with regard to vacuum available suction or centrifugation method, and compressed air or highly pressurised liquid also can be used for washing the reversed material of fusing.If but the casting model element is by the sublimator material manufacturing, micro structural component 100 is heated to the sublimation temperature of sublimator material, thereby sublimator material is through extracting passage evaporation removal from micro structural component 100 that the back forms by elongating the shape model element.If but the casting model element is by the soluble material manufacturing, specific solvent is through extracting passage that the back forms and can inject micro structural component 100 and soluble material is dissolved and flush out micro structural component 100 by elongating the shape model element.

In above-mentioned example, after model element was removed from micro structural component, upper strata inner chamber 102, lower floor's inner chamber 103 and path 10 4a, 104b, 105a and 105b just formed in micro structural component 100, and micro structural component 100 breaks away from from device mould 300 thereafter.

The mould body 301 of device mould 300 can be manufactured by steel or plastic processing.

The example of liquid polymer of micro structural component of being used to cast has the rubber of polyurethane polydimethylsiloxane (PDMS), Merlon polypyrrole, resin, teflon resin, epoxy resin, polymerization or the plastics of polymerization.Liquid polymer mixes a polymer substrate and curing agent by certain ratio.With the road. the Sylgard184 PDMS of peaceful (Dow.Corning) company of section is an example, blending ratio is 10: 1, polymerization time at room temperature is 48 hours, is 20 minutes under 100 ℃, thereby has duplicated features of microstructures in device mould 300 accurately in liquid polymers curing after the polymerization.

Additive or reinforce powder and can add the character of the polymer after the curing is changed to some extent, as change its hardness, density, impact strength, melt temperature, chemical stability, abrasion resistance, heat conductivity, electrical conductivity and electromagnetic wave shielding.

With reference to figure 4, device mould 300 is combined by mould body 301 and model element 210,310,302a, 302d and 312a,

312b.Model element

210 and 310 shapes are determined the shape of upper strata inner chamber 102 and lower floor's inner chamber 103 respectively.

Model element 210 supports and is fixed on an accurate position by 302a and 302b from both sides, model element 310 supports and is fixed on an accurate position by model element 302c and 302d from both sides,

model element

302a and 302b are an elongation shape model such as shaft-like shapes of having determined path 10 4a and 104b respectively, and model element 302c and 302d are an elongation shape model such as shaft-like shapes of having determined path 10 5a and 105b respectively.

Referring to Fig. 4 and Fig. 5, the part 320 of model element 302a is passed in the hole 303a on mould body 301 abutment walls 306, its end 322 is inserted in the sunk structure 212a on the model element 210, and other model element 302b-d also has identical combining structure with mould body 301 and model element 210 and 310.Backstay 312a is by the hole 314a on mould body 301, in hole on the model element 302a 316 and the hole on model element 302c 318, prevent that model element 302a and 302c move with respect to mould body 301 behind die assembly, equally, backstay 312b is used to prevent that model element 302b and 302d from moving with respect to mould body 301 behind die assembly.One key toothing 214a is arranged in sunk structure 212a, and a keyway arrangements 206a who is harmonious is with it arranged also in the end 322 of model element 302a, key toothing 214a and keyway arrangements 206a match behind die assembly, be used to prevent the mutual rotation of

model element

210 and 302a and move, at model element 210 and model element 302b, identical key tooth, keyway arrangements are arranged also between model element 310 and model element 302c and the 302d equally.If model element 210,310 and 302a-302d adopt to reverse the material manufacturing,

backstay

312a and 312b adopt the same material with mould body 310, and when liquid polymers injection device mould 300 and after solidifying, backstay 312a and 312b extract from device mould 300.Heating or change environmental factor, model element 210,310 and 302a-302d melt in micro structural component 100 and isolate.Inner chamber 102,103 and path 10 4a-b, 105a-b just form in micro structural component 100.In this example model element 302a-302d can be crooked and around planform, form channel design correspondingly thus.

If

model element

210 and 310 is by reversing material, soluble material and sublimator material manufacturing, and model element 302a-302d adopts metal and plastics manufacturing, when liquid polymers injection device mould 300 and after solidifying, backstay is extracted from device mould 300, thereafter model element 302a-302d extracts from device mould 300 two ends, thereby forms path 10 4a, 104b, 10Sa and

105b.Model element

210 and 310 dissolution with solvents that can be injected into or change environmental factor make it become liquid state or gaseous state is removed from micro structural component 100.Model element 302a-302d is straight or the shape of continuous bend can be extracted it after liquid polymers solidifies from micro structural component 100 and device mould in this example.

Isolate from micro structural component by reversing the model element that materials processing becomes, after model element dissolved liquefy, vacuum draw and centrifugal treating can be used for making model element to quicken to separate from micro structural component.

Barrier film 106 on after the space between

model element

210 and 310 is filled by liquid polymers and solidified, forming between the lower inner cavity 102 and 103.When compressed air puts on upper strata inner chamber 102, inner chamber 102 expands barrier film 106 is moved down.If be full of liquid in lower floor's inner chamber 103,106 move down just pushed liquid and flowed out from inner chamber 103.The micro structural component 100 of this multilayer inner chamber can be used for by a chamber in little valve of air operated or the wriggling Micropump.

Example shown in Fig. 1-4, two are

elongated shape model

302a and 302b supports location model element 210, and only one is elongated the shape model such as 302a also can support location model element 210.At this moment in the micro structural component 100 of casting, just have only a passage such as 104a to link to each other with inner chamber 102.

The process of a processing and manufacturing model element 210 shown in Fig. 6-8.Fig. 6 is the top view of component mold 200, and component mold 200 is used for casting processing.Fig. 7 is the cutaway view of component mold 200, and its section 7 is the plane vertical with the top.Fig. 8 shows another cutaway view of component mold 200, and its section is plane 8.

Referring to Fig. 6-8, component mold 200 is by mould body 201, and model element 204a and 204b and mould loam cake 208 combine.Model element 204a and 204b elongate the shape model element, as shaft-like.There are two hole 203a and 203b in mould body 201 two ends, and model element 204a and 204b pass this two hole 203a and 203b respectively.Mould body 201, mould loam cake 208 and model element 204a and 204b combination back form the shape that closed cavity 202 is determined model element 210 thus, and the inner surface 222 of component mold 200 is determined the shape of model element 210 bottoms 215, as shown in Figure 5.Inner surface 220 is determined the shape at model element 210 edges.And inner surface 224 is determined the shape on the top 217 of model element 210.

One key toothing 206b is arranged among the 203a of hole on mould body 201, have a keyway arrangements 206b and key toothing 206a to coincide mutually on the model element 204.This complementary structure can prevent the rotation of model element 204a when die assembly, thereby behind the assurance die assembly, the position of model element and form accurately, one has in identical structure and the mould body 210 structure in the corresponding aperture identical on model element 204b.The keyway that inserts part 206b in the cavity 202 in the mould body 201 on model element 204a has also played casting key toothing 214a in the depression of model element 210.There is being identical structure on model element 210, to form key toothing 214b on the model element 204b equally.Mould body 201, mould loam cake 208 and model element 204a, 204b can adopt metal, silicon and plastics to manufacture, and adopt micro fabrication or Sterolithograph technology.

Component mold 200 can have two openings, as hole 205a and the 205b that links to each other with dies cavity 202 on die cover 208.When adopting Shooting Technique processing and manufacturing model element 210, liquid reversed material or soluble material can be injected in the dies cavity 202 by one of these two openings.When the temperature reduction, the liquid state of injection can reverse material or soluble material is solidified in mould.When adopting stamping technique processing and manufacturing model element 210, the reversed material of pulverulence, soluble material or sublimator material are compressed in the dies cavity 202.After material cured of injecting or moulding, model element 210 is deviate from from component mold 200.

If the employing casting process is manufactured in the processing of model element 210, mould 200 does not need loam cake 208, but an open architecture, liquid reversed material or soluble material are directly poured in the mold cavity 202.If adopting drawing-die to make component mold 200 can be two-part structure.Model element 210 keeps the size of its mould after casting, and the process of curing is very little to the influence of physical dimension.If but a certain physical dimension dwindles, when designing mould 200, just can amplify mould 200 correspondingly-sized according to constriction coefficient in solidification process.

If model element 210 employings can reverse material and manufacture, model elements 210 therefrom melt and shift out after micro structural component 100 casting, and it can reverse material and can repeat to re-use.

Fig. 9 is a multi-channeled micro-structured device 400.Figure 10 represents to make the top view of these micro structural component 400 moulds 410, and Figure 11 represents that along the plane 11 cut the profile of device mould 410 shown in Figure 10 open, and Figure 12 represents that along the plane 12 cut the cutaway view of device mould 410 shown in Figure 10 open.

Referring to Fig. 9, multi-channeled micro-structured device 400 is microchannel electrophoresis devices, and by split tunnel 402, injection channel 403 and

liquid pool

406a, 406b, 407a and 407b form.The size of passage 403 is greater than the size of passage 402, and

passage

402 and 403 intersects at joint 404 places.Electrode can insert in the liquid pool from the top opening of

liquid pool

406a, 406b and 407a, 407b and also can be imbedded in to go in the liquid pool on bottom and the surrounding wall.Put on electrode to

liquid pool

406a and 406b at voltage, charged particle will flow to liquid pool 406b from liquid pool 406a in the sample, has just injected sample in the passage 403.When the voltage that applies changes to

liquid pool

407a and 407b, the sample particle at joint 404 places will flow to liquid pool 407b direction along passage 402 from liquid pool 407a.Because the electric charge of particle and the difference of quality, different particles are just separated in flow process gradually, by fluorescence, detection means such as electrochemistry have just realized the separation side of sample is analysed detect flowing of particle near liquid pool 407b place.

Referring to Figure 10-12, device mould 410 is combined by mould body 429 and some model elements, mould body 429 comprises at the bottom of the mould 422, limit wall 420a-420d, some

pillar

412a, 412b are being arranged on 422 at the bottom of the mould, 414a and 414b, they determine shape and the position of

liquid pool

406a, 406b and 407a, 407b respectively, model element comprises

filament

416 and 418, and they determine the shape and size of

passage

403 and 402 respectively.

Porose 421a of difference and 421b on

limit wall

420a and 420b, porose 426a of difference and 426b on

pillar

412a and 412b, filament 416 can therefrom pass.Respectively porose 424a and 424b on

limit wall

420c and 420d,

porose

430a and 430b respectively on

pillar

414a and 414b, porose 428 on filament 416, filament 418 can therefrom pass.Four jiaos have notch on

device mould

410, and 432a-432d is used for taking off of mould and puts.

As an example, the diameter of filament 416 is 100 microns, and the diameter of filament is 200 microns, and by the

passage

402 and 403 that two filaments are made, its diameter just is 100 microns and 200 microns respectively.

The combination of device mould 410 is finished by the following step, and the frame of limit wall 420a-420b combination is placed at the bottom of the mould on 422, and filament 416 is passed from

hole

421a, 426a, 426b and 421b, and filament 418 is passed from

hole

424a, 430a, 428,430b and 424b.

After the combination of device mould 410, liquid polymers is poured into by in the space 411 that forms behind the device die assembly, solidifies back filament 418 at liquid polymers and extracts from device mould 410, forms passage 402 thus in micro structural component 400.Filament 416 is extracted from device mould 410 subsequently, forms passage 403 thus in micro structural component 400.After multi-channeled micro-structured device 400 was deviate from from mould 410, upset made progress

liquid pool

406a, 406b and 407a, 407b opening in use.

From liquid pool 406a to limit wall 405d with the part 408 of passage 403, can be used for the transmission of liquid, if need not also they can be sealed from liquid pool 406b to limit wall 405b.Same from liquid pool 407a to limit wall 405c with the part 409 of the passage 402 from liquid pool 407b to limit wall 405a also can play effect that same liquid transmits or with its sealing.

Filament

416 and 418 can adopt metal, glass, carbon is very thin or aramid is very

thin manufactures.Filament

416 and 418 can be the filament of straight or continuous bend, so that they can therefrom be extracted after the micro structural

component casting.Filament

416 and 418 diameter or size are decided according to

passage

403 and 402 designing requirement.According to its size of needs of using can be from the millimicron to the millimeter scope.Can reverse material, soluble material, sublimator material and also can be used for the processing and manufacturing of filament.

The technology of making multilayer inner chamber micro structural component 100 and multi-channeled micro-structured device 400 can be used for the processing and manufacturing of microfluid micro structural component, and other micro element such as microsensor also can be adopted the manufacturing that uses the same method.Micro structural component also can obtain to use at biomedical aspect, as is used for the implantation micro-system of medical diagnosis or drug delivery.

Can be used for the integrated microfluid system of DNA analysis 900 referring to Figure 13-15,, it is made of two parts: microfluidic device 500 and cartridge 800, microfluidic device 500 comprise that device body 501 has the platform 600 of a microfluidic element and a function element in it.The technology of making micro element 501 is similar to aforesaid method, and a device mould is by a mould body, and a platform 600 and various model element combine.The model element of some model elements or part can adopt and can reverse material, soluble material or sublimator material manufacturing.

Microfluidic device body 501 can adopt device die casting liquid polymers to wherein making, and the aforesaid release method that is used for micro structural component also can be used for microfluidic device 500 is broken away from from the device mould.Platform 600 is included in integrated circuit, electrode, micro-heater, sensor and other function element on the circuit board 620.Fluid section comprises that in microfluidic device 500 sample loads liquid pool 526 (Figure 11), PCR reative cell 524, a wriggling Micropump 517 (Figure 18), a little valve 516 (Figure 19), a split tunnel 504, an injection channel 508, fluid interface 514a-d and pneumatic interface 518a (Figure 14).

Also comprise in the microfluidic device 500 and detecting and control section, as circuit board platform 620, laser diode 530, micro optical lens 532, integrated circuit 536, micro-heater 522, temperature sensor 528, electrode 512a-512d, electrode group 534, ring-shaped heater 604, convex memorial alloy barrier film 602, electric connector 506.Temperature sensor 528 is integrated in the PCR reative cell 524, and micro-heater 522 places under the PCR reative cell 524.Electric connector 506 provides the electric interfaces of each electronic devices and components, as laser diode 530, micro-heater 522, temperature sensor 528, electrode group 534, ring-shaped heater 604 and electrode 512a-512d.Photoconductive channel 502 and 503 (Figure 24) is integrated in the detection that is used in the microfluidic device 501 fluorescence excitation.

Cartridge 800 (Figure 13 and Figure 28) comprises a bottom 801a and frame 801b, electrical outlets 802 is arranged on the 801a of bottom, with electric connector 506 interfaces in microfluidic device 500, there is pneumatic interface 814a-814c to cooperate on the frame 801b with the pneumatic interface 518a-c of peristaltic pump 571 in the microfluidic device 500, fluid interface 812a-812d cooperates with fluid interface 514a-514d in the microfluidic device 500, electric interfaces 808 is connected with electrical outlets 802 on the 801a of bottom with 810, and optical inductor 804 is relative with photoconductive channel 502 in the microfluidic device 500.

Below description stated the analysis of using 900 couples of DNA of microfluid system, buffer solution injects microfluidic device 500 all reative cell, liquid pool and passage by fluid interface 514c.The sample of DNA injects sample filling liquid pool 526 after sucking pipettor, and Micropump 517 is drawn onto PCR reative cell 524 from liquid pool 526 by passage 521a with the sample of DNA, and sample is done the thermal cycle chain reaction in PCR reative cell 524.The temperature of sample is by micro-heater 522 and temperature sensor 528 controls in PCR reative cell 524.Micro-heater 522 and temperature sensor 528 are linked integrated circuit 536 again.This integrated circuit 536 can be a chip microprocessor, realizes the temperature control in the PCR course of reaction thus, subsequently, reacted sample by micro-creep pump 517 pumps in the liquid pool 710 of little valve 516.Micropump 517 comprises three sub-pump chambers 513, and each pump chamber 513 is by pneumatic interface 518a, and pneumatic chamber 519a and liquid chamber 520a form.Pneumatic interface 518a-c links to each other with pneumatic interface 814a-c on cartridge 800, is connected to outside pneumatic operated valve and compressed air (not expression in the drawings) subsequently.

The structure of little valve 516 as shown in figure 19, liquid pool 710 links to each other with the liquid pool 510b of passage 504 and potting by injection channel 508.The liquid pool 510a of potting links to each other with the liquid pool 510c of potting by split tunnel 504, and injection channel 508 and split tunnel 504 cross at point 505 places.The liquid pool 510a-c and 710 of electrode 512a-d and potting integrates.Apply a voltage (as 300v) between electrode 512d and 512b, carry sample and flow to liquid pool 510b from liquid pool 710 thereby in passage 508, produce electro-osmosis stream (or electrophoresis stream).When voltage (as 1000v) turns between electrode 512a and the 512c, in passage 504, produce electro-osmosis stream (or electrophoresis stream), thereby the sample at joint 505 places flows towards the direction from liquid pool 510a to 510c, just is separated from each other because the difference of quality that DNA shears and electric charge DNA in flow process shears.The technology that detects the DNA shearing adopts the laser-Induced Fluorescence Detection of Capillary Electrophoresis.In the PCR reaction, the DNA sample is fluorometric reagent on the mark just, laser 530 focuses on the zone 529 of split tunnel 504 near liquid pool 510c, when DNA shears by the laser focus point, is just sent the fluorescence of certain wavelength by the fluorescer of mark in the DNA shearing of laser excitation.If the emission wavelength or the intensity of laser diode 530 are not suitable for fluorescence excitation, flexible method is to adopt outside laser instrument, at this moment directly project the zone 529 of passage 504 after laser instrument can focus on from the bottom of microfluidic device 500 or, after lens 532 focusing, project on the passage 504 then by the photoconduction of potting microfluidic device 500 in.

Aspect fluoroscopic examination, the photoconduction 503 of an O shape, is accepted fluorescence to greatest extent and is delivered to photoconduction 502 around passage 504 at regional 529 places, is projected at the optical inductor 804 on the cartridge 800 then.Before optical inductor 804, can there be one or one group of filter to select wavelength of fluorescence, just can detect DNA thus and shear and sequence.In microfluidic device 500 integrated Capillary Electrophoresis and laser lead thoroughly fluoroscopic examination realized to DNA shear fast, high-resolution, highly sensitive detection.

The detection that DNA shears also can be adopted the method for electrochemical analysis.One group of electrochemical electrode 534 potting are in the zone 535 of split tunnel 504, because DNA shears by surveyed area 535 and produces electrochemical reaction, the signal of telecommunication that electrode detection obtains or loses to electronics, and be delivered to integrated circuit 536 on chip and amplify and handle.

One group of electrochemical electrode 534 comprises three electrodes (as Figure 22): 754, one counter electrodes 752 of 756, one reference electrodes of a working

electrode.Electrode

754 and 756 is miniature ring electrode (as Figure 23), and the interior annular aperture of electrode or size equal the diameter or the size of passage 504, and the inner surface of

electrode

754 and 756 interior annular aperture and passage 504 merges.Passage 504 joins with the vertex of a cone of conical cavity 750, receive potting liquid pool 510c then, electrode 752 is pointed electrodes, place the cone top part of taper chamber 750, the exit of passage 504, electrode group 534 is installed on the circuit board 620, and is connected to integrated circuit 536, and electrochemical signals is amplified and processing.

As an example, the passage 515a-515c of limit wall from liquid pool to microfluidic device body 500, the interface that can be used for liquid links to each other with 508 passage 504 with corresponding interface on the cartridge 800.Liquid is injected the liquid pool and the passage of microfluidic device 501 or cleaning microfluidic device 500 inside.

Figure 15 represents the perspective view of integrated platform 600, and platform 600 comprises a circuit board 620 and electronics and the optics fixed on it.

Referring to Figure 16, flow process 910 is to adopt the microscopic model element to manufacture the process of micro-structural in a solid structure, and it comprises the following steps:

Step 31, the processing and fabricating of component mold.Component mold 200 is to be used for casting model element 210, and it can be used to manufacture the pneumatic chamber 519a-519c of Micropump 517.Another component mold is used for the processing that casting model element 310 also can be used for Micropump 517 liquid chamber 520a-520c, same other component mold can be manufactured and be made up, the processing that is used for other model element is manufactured, to be implemented in the micro-structural that forms other in the microfluidic device body 501.

Step 32, the casting model element.Can reverse material, soluble material or sublimator material and be poured into, inject or be compressed into the component mold of being manufactured and being made up by step 31, after material cured, model element is the demoulding from component mold.

Step 33 is made and the assembling device mould.Be used to cast the device mould of microfluidic device 500 by the mould body, various model elements and an integrated platform 600 combine.Be used in structure

inner chamber

519a and 520a in the microfluidic device 500 as

model element

210 and 310,

filament

416 and 418 also can be used for constructing passage 504 and 508.Model element 742 (as Figure 21) can be used for constituting the liquid pool 510a-510c of potting, and the device mould can be that the structure of an opening is used to pour into a mould manufacturing microfluidic device 500 or the structure of a sealing is used for the injection molding manufacturing.

Step 34, the device mould inner surface is handled.For prevent some liquid polymerses after curing with mould body or model element bonding, destroy accuracy, the integrality of structure, improve the yield rate of product, on the mould body inwall of device mould and model element, be coated with releasing agent.Have some liquid polymerses not bonding with other material, as PDMS, this procedure of processing can be omitted so.

Step 35, the casting microfluidic device.Liquid polymers is poured into or the injection device mould, is filled in the space that is stayed by mould body and model element in the device mould.

Step 36 shifts out device mould and microfluidic device with model element after liquid polymers solidifies.When model element (as 210 and 310) is supported by shaft-like model element (as 302a and 302d), earlier with shaft-like model element fusing or extract the device mould.The shaft-like model element that shifts out produced one in microfluidic device 510 from outside lead to internal model element (as 210 and 310) passage (as 104a and 105a).Microfluidic device 501 is heated to the solution temperature of model element, after the model element dissolving, by adopting vacuum draw and centrifugation method, model element is shifted out microfluidic device 501; Perhaps inject solvent model element is dissolved, it is flushed out microfluidic device 501, can adopt vacuum draw and centrifugation method to accelerate the process that model element breaks away from the flushing by the passage that stays by shaft-like model element.Ultrasound bath also can be used for the removing of solubilized model element.

Step 37 breaks away from microfluidic device from the device mould.

Use chip lab or little bulk analysis system, can make the processing of sample integrated, realized operation, reaction and detection integrated of sample and reagent.

Microfluid system 900 is the integrated electrophoresis analyzers of a single-chip, and it has comprised fluid-operated, PCR chain reaction, laser-Induced Fluorescence Detection and Electrochemical Detection.In microfluid system 900,8 funtion parts are arranged.(a) sample application of sample liquid pool 526; (b) PCR reative cell 524 and heater 522 and heat sensor 528; (c) three grades of wriggling Micropumps 517; (d) Micropump 516; (e)

microchannel

504 and 508 of compartment analysis; (f) electrode 510a-d; (g) laser diode 530 that detects of LIF (LIF), lenticule 532,

photoconduction

503 and 502 and optical light filter 806, optical inductor 804; (h) the electrode group 534 of Electrochemical Detection and the interlock circuit in 536.

Referring to Figure 17, sample application of sample liquid pool 526 is by the 704 access road 521c of fluid chamber, and exit passageway 521a forms with the V-arrangement funnel 702 that is connected fluid chamber 704, and exit passageway 521a is connected to PCR reative cell 524 (as Figure 18), when application of sample, inhaling has the pipette top of sample to pass V-arrangement funnel 702.After sample adds fluid chamber 704,517 work of wriggling Micropump, sample sucks the PCR reative cell by exit passageway 521a.Access road 521c is connected to fluid interface 514c, is used for the cleaning of microfluidic device 500 inner fluid devices and the injection of buffer solution.

The top 700 of funnel is the aperture 701 that is made of elastic membrane 703, passes V-arrangement funnel 702 when the top of pipette, and top aperture 701 is opened, and sample adds fluid chamber 704.When liquid enters fluid chamber 704 from access road 521c, the pressure in the fluid chamber is greater than the pressure of outside, funnel elastic membrane 703 pressurizeds and funnel top aperture 701 is closed.Prevent like this outside the liquid that access road 521c enters flows out to funnel 702.

The pneumatic chamber 519a-c of PCR reative cell and Micropump 517 and liquid chamber 520a-c are constructed by model element.The model element 210 that its shape and Fig. 5 describe is similar, and one is elongated the shape model element, is used for the model element of these chambers of structure worn as filament or elongate bars connecting together.At casting microfluidic device 500 and after solidifying, elongate the shape model and from microfluidic device 500, extract, form passage such as 521a-521d.After model element cleaned out microfluidic device 500, passage 521a-521d was fluid interface 514c, application of sample liquid chamber 704, and PCR reative cell 524, the liquid chamber 520a-c of Micropump 517 and the liquid pool 710 of little valve 516 link together.In addition, three model elements of three elongation shape model supports are used to construct three pneumatic chamber 519a-c and interface 518a-c.

Referring to Figure 18, the work of little shape peristaltic pump has one of four states: state one,

pneumatic chamber

519a and 519b venting; The 519c inflation.State two, pneumatic 519a inflation; 519b and 519c venting.State three, 519a and 519b inflation; The 519c venting.State four, the 519a venting; 519b and 519c inflation.By the coherent inflation and the venting of these four sequences, pneumatic chamber extruding corresponding liquid chamber pumps into liquid pool 710 with liquid.

Referring to Figure 19, the action of little valve 516 is finished by arch memorial alloy (SMA) diaphragm 602, diaphragm 602 by a ring-shaped heater 604 around, aperture 716 is arranged on diaphragm 602.Electric current puts on heater 604 through circuit wafer 620 and connector (not expression in the drawings).Connector not only plays the effect of electrical connection, also plays the effect of support simultaneously, and ring-shaped heater 604 and SMA diaphragm 602 are supported on a fixed position.Little valve 516 also comprises lower floor's liquid pool 710, upper strata cavity 718, interface channel 712 and top blow vent 714.Bottom electrode 512d at lower floor's liquid pool 710 is connected to circuit board 620 through pillar 722, and electrode 512d is used for the liquid in the liquid pool 710 is applied voltage.

The work of little valve 516 has two states: state one, closing passage 712; State two is opened passage 712.When electric current is applied to heater 604, diaphragm 602 heating cause diaphragm 602 to be bent downwardly, and shown in dotted line among Figure 19 715, its middle body 713 will connect up and down that the passage 712 of chamber seals.After electric current was removed, heater 604 cooled down, and diaphragm 602 returns to its original shape, and both diaphragm 602 was bent upwards, as the solid line among Figure 19.The passage 712 of chamber is open about connecting like this.

When sample or liquid through application of sample liquid pool 526 through PCR reative cell 524 pumps to lower floor's liquid pool 710, little valve 516 is operated in its normality, the state of both having opened.Lower floor's liquid pool 710 is through passage 712, upper strata cavity 718, and aperture 716 and blow vent 714 on the diaphragm 602 lead to atmosphere, and at sample or liquid pump during to liquid pool 710, because the opening of passage 712, sample or liquid just can not flow to passage 508.And when little valve cut out, promptly passage 712 was closed, and the liquid pump then flows to passage 508 behind liquid pool 710, and this can be used for the cleaning of passage and liquid pool and the adding of buffer solution.Liquid flows out microfluidic device 500 through

fluid interface

514a, 514b and 514d.

Little valve 516 and memorial alloy dome-shaped diaphragm 602 thereof and ring-shaped heater 604 have been represented the example of an integrated mechanical organ in microfluidic device 500.Little valve 516 also can be simply by pneumatic chamber squeezing passage, and as constructing a pneumatic chamber around passage 712, the inflation of its pneumatic chamber and venting reach the function of closing with open channel 712.

Referring to the potting liquid pool 510a that is integrated with electrode 512a shown in Figure 20,

liquid pool

510b and 512c also are integrated with the bottom that

electrode

512b and 512c, electrode 512d place the liquid pool 710 of little valve 516 respectively.

Because

passage

504 and 508 is small-sized, manufacture in the process at microfluidic device 500, after liquid polymers solidifies, model element be removed quite difficulty by

passage

504 or 508 from microfluidic device 500.The passage 515a of an expansion is built into and connects the zone of liquid pool 510a to fluid interface 514a.

Figure 21 has represented that the wherein part of the device mould 920 of a structure microfluidic device 500 is used to constitute structure shown in Figure 20, device mould 920 is made of a row element, a model element 742, an electrode 512a, the part of circuit board 620, filament 746, pipe 744 and mould body 740.Model element 742 has the shape with potting liquid pool 510a complementation, the internal diameter of pipe 744 or inside dimension equate with the diameter or the size of filament 746, filament 746 inserts among the pipe 744, both are by the hole 748 on mould body 740, one end of pipe inserts among the model element 742, and filament 746 passes model element 740 and other model element is worn linked up.At casting micro structural component 501, after liquid polymers solidified, filament 746 was at first extracted, and has constructed passage 504 in micro structural component 501.Pipe 744 is extracted from micro structural component 501 again, constitutes passage 515a, and its internal diameter or size are greater than passage 504, and it is just relatively easy like this model element 742 to be cleared out of micro structural component 501, and big channel size is easier to constitute external fluid interface.

Referring to Figure 22 and 23, electrochemical electrode group 534 comprises

ring electrode

754 and 756 in two passages, with a tunnel ends electrode 752, electrode group 534 is used for the Electrochemical Detection of separating in the end of passage 504, wherein electrode 756 is a working electrode, 754 is reference electrode, and 752 counter electrodes, Figure 23 have been represented the structure detail of one of them electrode 756 with passage 504.As seen from the figure, the interior ring of ring electrode 756 merges mutually with passage 504, is formed in the detection in the microchannel 504.In separation process, the variation of fluid chemistry composition is converted into the signal of telecommunication and is detected by electrode group 534, links to each other with integrated circuit 536 on circuit board 620 by the pillar lead of electrode, carries out the amplification and the analysis of signal.

Electrode 752-756 is integrated into being described below among the micro structural component 500:

Electrode 752-756 is separately fixed on its lead pillar 534a-534c, and be assembled on the circuit board 620, its ring electrode 754, the summit of 756 central point and needle electrode 752 and passage 504 are point-blank, the model element filament 746 of structure passage 504 passes the centre bore of

ring electrode

754 and 756, and the vertex of a cone of the cone-shaped model element that is used to constitute conical internal cavity 750 and liquid pool 510c is inserted in its end.In the electrode 752 wedging cone-shaped model elements, behind the micro structural component 500 of having cast, filament model element 746 is therefrom extracted, and model element is removed from micro structural component 500, and electrode 752,754 and 756 constitutes electrochemical detection system with regard to potting among micro structural component 500.

Referring to Figure 24, laser-Induced Fluorescence Detection is by laser diode 530, lenticule 532, and O shape photoconductive channel 503 and photoconductive channel 502 are finished.Lenticule 532 supports by 760, and the laser beam that laser diode 530 produces focuses in passage 504 through lenticule 532, and the fluorescence labeling Stimulated Light that has on the fluorescently-labeled sample of separation excites generation fluorescence.O shape photoconductive channel moral idea 503 is collected the fluorescence that sample sends to greatest extent around passage 504.There is an aperture 762 that laser beam can be passed through at O shape photoconductive tube in the face of lenticule 532 places.If the intensity of laser diode 530 or wavelength can not satisfy the requirement of laser fluorescence, laser beam can produce by outside laser instrument, injects microfluidic device 500 from the bottom of microfluidic device 500.The reflective mirror that at this moment one 45 degree can be installed in the position of laser diode 530 throws light beam to passage 504.Laser beam also can directly project passage 502 from the bottom.At this moment condenser lens 532 also can be placed in the following outside of microfluidic device 500.And also should there be an aperture that allows light beam pass through in the hole 762 on O shape photoconduction mutually also over against the bottom on circuit board 620.

Photoconduction

502 and 503 is used to collect and transmit fluorescence to the optical sensor on cartridge 804, adopts aforesaid model element to form the method for cavity in micro structural component, can construct

photoconduction

502 and 503 passages in microfluidic device 500.Filling refractive index within it is greater than the liquid that constitutes microfluidic device 500 materials after photoconductive channel constitutes.A liquid light guide has just constituted.If the optical index of the material of formation microfluidic device 500 is bigger, at this moment can in photoconductive channel, plate one deck refractive index materials with smaller, as Teflon AF resin.The refractive index that guarantees fill liquid greater than with the material of its boundary.

Figure 25 is and the top view of the cartridge 800 of microfluidic device 500 interfaces, and cartridge 800 is included in three pneumatic interface 814a-814c of its side, and it is corresponding with the pneumatic interface 518a-518c of peristaltic pump in the microfluidic device 500.Fluid interface 812a-d is corresponding with the fluid interface 514a-514d in the microfluidic device 500.At each interface, there is an O shape ring recess 816 to be used to install O shape circle, prevent the leakage of gas or liquid.

At the bottom of cartridge 800 801a joint 506 interfaces in electric interfaces 802 and the microfluidic device 500 are arranged, interface 802 links to each other with 810 with the electric interfaces 808 of cartridge 800 sides.810 are used for the connection of high-tension electricity, and high-tension electricity is applied as electrode 512a-512d.Interface 808 is used to measure and being connected of control signal.

Optical sensor 804 is installed in the side 801b of cartridge 800, and a light filter plate 806 places before the optical sensor 804, is used to stop scattered light, and allows the light of wavelength of fluorescence pass through.Four jiaos in cartridge 800 have fixed screw 818.Cartridge 800 provides microfluidic device 500 and extraneous interface.Make microfluidic device 500 be convenient to operation and detection.More expensive or compatibility is not suitable for being integrated into the components and parts in the microfluidic device 500 owing to price, all adapts to place on the cartridge 800.These components and parts can be microprocessor, high-power light source, optical sensor and other optical element.Because these crucial components and parts closely link to each other with microfluidic device 500, improved the sensitivity that detects thus, improved the global reliability of system, reduced the volume and the power consumption of system.

Integrated microfluid system 900 can make system's miniaturization of chemistry, biology and medical analysis.The direct advantage of bringing is that the consumption of sample and reagent reduces.System can realize portable, and fluid chip wherein can be disposable chip.And the machining manufacture of micro structural component of the present invention, broken traditional little processing essential bonding technical process, the micro structural component that processing and manufacturing forms is a whole single chip architecture, wherein do not have liquid to the mutual leakage between external leakage and the micro-structural.Micro-structural in the microfluidic device 500 can be different shape and size, does not have the restriction of the length and width height ratio of traditional micro fabrication.The micro structural component of being made by the present invention obviously improves as the q﹠r of microfluidic device 500, and the yield rate of product is also significantly improved.

Processing technology of the present invention need not to have simplified technological requirement between the required super cleaning of conventional semiconductor industry and little processing, has reduced the up-front investment of product cost and factory.And the used liquid polymers of processing technology of the present invention is lower with respect to traditional material such as silicon, slide, and this also greatly reduces product cost.Microfluidic device is a kind of consumptive utensil.Adopt with cartridge 800 structures of its interfaces device that some costs are higher from microfluidic device 500 in the mobile cartridge 800, making microfluidic device 500 can be once utensil, but because the integrated and integrated performance that can not lose system again.

Make liquid polymers structure micro structural component reduce the cost of chip as previously mentioned, liquid polymers also has hypotoxicity or avirulence and good biocompatibility in addition, make micro structural component not only can be used for biomedicine and chemical analysis, and can be used to implant the sex medicine instrument.The chemical inertness of liquid polymers in addition, the soft and patience of diversified surface characteristic and mechanism, all make micro structural component by the liquid polymers structure can be used for various chemistry, biology and medical science detect and handle, synthetic.The microfluidic device that also can be used for simultaneously the property implanted.Some liquid polymerses also have good optical property, make micro structural component can be used for analyses such as fluorescence, spectrum.Because electrode is integrated, makes micro structural component also can be used for the analysis and the detection of electrochemistry and bio-impedance.

The present invention also can be used for the detection of food and environment except can be used for analytical chemistry, biological diagnosis, medical diagnosis, the detection of biological warfare and medicine and screening.Aspect commercial measurement and control, method of the present invention also can be used for constructing microsensor and little transducer.

Though method of the present invention and some application examples are as preceding statement, some other methods and applications example also can be realized in claim scope described later.For example, in Figure 13, can be with sensitivity and the suitable surveyed area 529 of optical sensor potting in microfluidic device 500 of volume, the fluorescence of induced with laser is directly detected.Part photoconductive channel in optical sensor in cartridge 800 804 and the microfluidic device 500 just can omit like this.Because optical sensor further near detecting target, is added integrated suitable lenticule, at this test point, the detection sensitivity of fluorescence will further improve.Microfluid system 900 carries out fluorescence analysis except can be used for to the shearing of DNA, also available protein, electrolyte and other biochemical composition is analyzed.If on the dna marker ultraviolet mark, system also can be used for ultraviolet absorption spectra analysis.

The material that foregoing model element uses can be to reverse material, soluble material or sublimator material, if use by solid-state reversed material or the sublimator material that is converted into liquid state or gaseous state, can under certain environmental condition, manufacture, encapsulate, the device mould is assembled and micro structural component is carried out liquid polymers casting model element.After liquid polymers solidifies, change environmental condition and make model element be converted into liquid state or gaseous state by the formed solid element, just can from micro structural component, separate.A simple example, can pour in the component mold by water, place and become solid-state ice under the low temperature, with the ice model element demoulding at low temperatures of moulding, and under low temperature environment the assembly device mould, the casting micro structural component, after the liquid polymers of casting micro structural component solidifies, it is moved on under the normal temperature environment, and the ice model element in the micro structural component melts, thereby separates from micro structural component.Environmental condition can be temperature, air pressure, magnetic field and light.If any material when being exposed to ultraviolet ray, can be from the solid-state liquid state that is converted into.So, manufacture at model element, can under no ultraviolet environment, carry out in the casting manufacturing of assembling of device mould and micro structural component, after finishing the micro structural component casting, be exposed to ultraviolet ray and just model element can be melted and from micro structural component, separate.

Microfluid system 900 is except can being used for microfluidic process and analyzing, also can be integrated with the solid-state holder that is used for microarray, on holder, form micro-cavities and passage, constituting probe molecule fixes, incorporate microarray chip is matched in the loading of sample, the hybridization of purification process and molecule.

Micro-structural of the present invention processing and the integrated method of micro-system not only can be used for microfluid system, and can be used for the processing and manufacturing of other any micro-structural system.

Claims

1. method of making micro structural component, comprising a model element of combination and a mould body is a device mould; From micro element of device die casting; From micro element, remove model element; And the demoulding.

2. in claim 1, adopt liquid polymers from device die casting one micro structural component.

3. in claim 2, liquid polymers can add additive or particulate to change its characteristic.

4. in claim 2, liquid polymers comprises polyurethane, polydimethylsiloxane, Merlon, polypyrrole, resin, teflon resin, epoxy resin, the rubber of polymerization or the plastics of polymerization.

5. in claim 1, the physical dimension of model element is less than 5 millimeters.

6. in claim 1, but model element can be rigidity model or casting pattern.But the casting pattern element can adopt and can reverse the material manufacturing; The model element that it is solid-state can be from the solid-state liquid state that transfers to when one or more environmental factors change.

7. in claim 1, model element can be by cured, gel, fusible alloy, eutectic alloy, resin, lipid or amine salt manufacturing.

8. in claim 1, after the micro structural component casting, therefrom remove model element and can comprise the one or more environmental factors of change, thereby can reverse the material model element from solid-state liquefy.

9. in claim 8, remove model element and can comprise applying centrifugal force or vacuum draw, separate the liquid model element in the micro structural component.

10. in claim 1, model element also can adopt the sublimator material manufacturing, can be from the solid-state gaseous state that transfers to when environmental factor changes.

11. in claim 10, remove model element and can comprise and change one or more environmental factors, so model element changes gaseous state into and separates from micro element from solid-state.

12. in claim 1, model element can also adopt the soluble material manufacturing, it can form a solid-state shape also can be by a specific dissolution with solvents.

13. in claim 1, the shape complementarity of the shape of model element and the micro-structural of constructing in micro structural component just is formed in the micro structural component in the shape of model element after separating model element from micro structural component.

14. in claim 1, model element can comprise an element that elongates shape and be used for forming a microchannel at micro structural component.

15. in claim 1, model element can adopt the component mold manufacturing, its shape and the model element shape complementarity that will make.

16. in claim 15, adopt component mold modeling element can material casting or injection element mould with liquid state in, change one or more environmental factors and liquid material become be solid-state or gel, break away from from component mold then.

17. in claim 15, adopt component mold modeling element dusty material can be pressed into model element, break away from from component mold then.

18. a method of making micro structural component comprises a set of model element and device set of molds are fitted together; The casting micro structural component and; From micro structural component, model element is taken out.

19. in claim 18, the casting micro structural component comprises that casting or injection molding liquid polymers are in the device mould.

20. in claim 18, a set of model element comprises two model elements, the shape of first model element is used for producing first cavity at micro structural component, and the shape of second model element is used for producing second cavity at micro structural component; Certain interval is arranged between first and second the model element when assembly jig, thereby form a flexible barrier film between two corresponding cavitys in micro structural component.

21. in claim 18, a set of model element comprises two and elongates the shape model element, the size of first model element or diameter are less than second model element, and the centre of the model element second has an aperture can pass first model element; When the assembly device mould, first model element is passed in the aperture on second model element and forms one and cross, and after the micro structural component casting, two are elongated the shape model elements and remove from device, have just formed two passages with joint in device.

22. in claim 18, a set of model element also can comprise one and elongate shape model element and a tubular model element, the inside dimension of tubular model element or internal diameter are consistent with the size or the external diameter of elongation shape model element; When assembly jig, elongate the shape model element and insert in the tubular model element, after removing mould, in micro structural component, just formed the passage of a size or internal diameter varies.

23. in claim 18, one set of model element also can comprise the model element that can cast and an elongation shape model element, the model element that can cast is used for being used to form a passage that connects cavity from the outside at identical shaped cavity of micro structural component structure and elongate the shape model element; It is an end that is used to accept to elongate the shape model element that but a dolly dimple is arranged on the casting pattern element.One key tooth is arranged in dolly dimple, at an end that elongates the shape model element corresponding keyway is arranged, this key teeth groove structure is used for preventing both moving mutually or rotating when mould is assembled.

24. in claim 18, one aperture is arranged on the wall of device mould body, but an end that elongates the shape model element inserts the depression on the casting pattern element, the other end passes the aperture on the wall, also have corresponding key toothing and the keyway that elongates on the shape model element to be harmonious in the aperture, model element rotates or moves when preventing the mould assembling.

25. in claim 18, the aperture on device mould body wall has played the purpose of support model element and fixed model position of components.

26. in claim 18, a set of model element can comprise a column structure, when model element was assembled, the column structure model element played the effect of support elongated shape model element, made it be fixed on the position of design.

27. a method of making the micro-structural integrated device comprises that combination one set of model element and overlaps function element and forms the device mould; The casting micro structural component; Disjunctive model element from micro structural component and reservation function element are in micro structural component.

28. in claim 27, the casting micro structural component comprises that casting or injection molding liquid polymers are in the device mould.

29. in claim 27, but a set of model element comprises a casting pattern element and a cover function element and comprises electrode, when the assembling device mould, earlier but electrode is imbedded in the casting pattern element, after the micro structural component casting, but the casting pattern element therefrom separates, but and the electrode that buries just is fixed in the cavity that stays after the casting pattern element separates.

30. in claim 27, but a cover casting pattern element comprises an elongation shape model element and a cover function element and comprises ring electrode, the size of ring electrode interstitial hole and the tangent plane consistent size of elongating the shape model element, when the assembling device mould, the interstitial hole that the shape model element inserts ring electrode will be elongated.Behind the casting micro structural component, from micro structural component, separate and elongate the shape model element, ring electrode is just imbedded in the micro structural component and with the passage that is formed by elongation shape model element and is contacted.

31. in claim 27, a set of model element forms passage in micro structural component, its passage can be used for the liquid light guide passage, smears one deck refractive index less than the liquid refractive index that is fed in the passage on channel surface, just forms the liquid light guide passage.

32. a device comprises, has the micro structural component body of microfluidic channel and cavity; Be imbedded in the micro structural component with passage and cavity in liquid contacting electronic element and the electronic device that is attached thereto; Be imbedded in the optics that transmits and accept light in the micro structural component.

33. in claim 32, the micro structural component body is made by polymer.

34. in claim 32, comprise a fixedly platform of electronics and optics ad-hoc location in the micro structural component.

35. in claim 34, this platform can be a circuit board.

36. in claim 32, the passage that is formed a cavity and be attached thereto by aforesaid method in micro structural component is equipped with a heater in cavity bottom, is used to heat the liquid that injects in the cavity, heater is by the little processing controls that is imbedded in the device; Also be equipped with temperature sensor in the cavity, and link to each other, thereby realization is to the control of fluid temperature in the cavity with microprocessor.

37. in claim 32, optics integrated in micro structural component can comprise, lens, photoconductive channel, and optical sensor.

38. in claim 32, the passage of micro structural component and cavity can comprise cavity and passage between inlet and cavity of a little valve, opening part at passage has a diaphragm, can reach by moving of matrix and to open or the purpose of closing passage, and this matrix can be the memorial alloy sheet.

39. in claim 32, the passage of micro structural component and cavity can comprise a fluid intake and a cavity, fluid intake is a funnel channel of inserting cavity, the part that funnel inserts in the cavity is a springform channel design, the funnel opening bigger from top is to the springform passage, its size is tapered, when fluid from outside enters cavity by inlet, this opening is opened, and when the pressure in the cavity during greater than the pressure of outside, this opening pressurized and closing, the fluid intake of realizing this unidirectional control can be to be realized by a film formed funnel shaped structure of elasticity.

40. a microfluid system, comprise a microfluidic device and with the cartridge of microfluidic device interfaces.

41. in claim 40, microfluidic device comprises pneumatic element, electronic component, and optical element; With comprise in the cartridge of microfluidic device interfaces with microfluidic device in the interface and the corresponding components and parts of pneumatic element coupling, with the interface of electronic component in microfluidic device coupling and corresponding device and with microfluidic device in the interface and the respective optical element of optical element coupling.

42. the device mould of a structure micro structural component comprises the mold of assembling device mould, the function element of the model element of assembling device mould and assembling device mould.

43. in claim 42, mold, model element and the function element of device mould are combined and are fixed in its design attitude when the assembling device mould, after the device casting, model element separates from the device mould with mold, and function element is integrated among the device.

44. in claim 42, but the model element of device mould comprises a cover casting pattern element, wherein have the first group model element and the second group model element, the first group model element is used for forming first group of cavity and passage at micro structural component, the second group model element is used for forming second group of cavity and passage at micro structural component, the position of first group of cavity and second group of cavity is a counter structure up and down, the middle elastic diaphragm that forms.

45. in claim 42, the mold of device mould go to the bottom and frame on some apertures are arranged, the position in its hole is used to determine when the device die assembly, the position of model element and function element.